PROJECT SUMMARY: Abnormal gene expression or abnormal sensory experience during development has a profound and permanent impact on the construction of brain circuits. Many developmental diseases likely do not arise from a single defect that is present in all sufferers, but rather from the systems-level impact of the interaction of any number of malfunctioning circuit elements. In order to understand how the elements of brain circuits interact during development and to shed light on how these processes go awry in diseases or injuries, it is important to investigate whole systems in the intact, living brain. To this end, we have developed a system via which we can study how individual mammalian cortical neurons change their properties when the circuit is modified by behaviorally relevant stimuli. This application proposes studies of the circuit mechanisms underlying the experience-dependent development of motion selectivity in the ferret visual cortex. At the time of eye opening, ferret visual cortex exhibits orientation selectivity and orientation columns, but neurons are not yet selective for direction-of- motion, a property of most mature neurons in this species. Motion selectivity (that is, direction selectivity) arises in the days and weeks following eye opening, and requires visual experience. However, recent experiments show that this experience has a primarily permissive influence on development, in that many parameters such as direction preference angle and speed tuning are primarily determined before the onset of visual experience. The first aim addresses the degree to which the activity in the cortex before eye opening determines the tuning parameters that can be uncovered through visual experience. We will provide animals with artificial experience with carefully designed ?arbitrary? patterns to examine how tuning parameters can be modified. Alternatively, the activity in cortex before eye opening may itself be permissive and activity-independent factors may determine tuning parameters. The second aim tests a novel hypothesis about the development of functional connections in early development. The classic idea is that connections are substantially overproduced and that experience and plasticity serve to prune inappropriate connections. Instead, we will test the idea that receptive fields start out small and grow in a manner that is largely determined at the onset of visual experience. The third aim directly examines the functional connections between LGN and cortex that might underlie direction selectivity and its development. Concurrently with the aims, a computational model of the ferret visual cortex will be constructed to illuminate the possible combinations of synaptic plasticity rules and initial circuit structure that could underlie the development of direction selectivity and speed tuning.